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This technique has the clinical potential to eliminate the inheritance of mutations in mitochondrial DNA that cause multiple diseases in the children of parents conceiving by in-vitro fertilization.

“Through this study, we have shown that it should be possible to prevent the inheritance of mitochondrial disorders,” said Dr. Dieter Egli, co-lead author of the study which appears today in Nature. (“Nuclear Genome Transfer in Human Oocytes Eliminates Mitochondrial DNA Variants”).

Egli, a Senior Researcher at the NYSCF, was joined in a conference call this past Monday to discuss the breakthrough by his co-lead author, Dr. Daniel Paull, also at NYSCF Laboratory and Dr. Michio Hirano of Columbia Medical Center.

“Mitochondria generate 90 percent of the body’s ATP energy from fats and carbs,” said Hirano. “They contain their own DNA, which encodes only 37 of the 20,000-plus genes in the individual.

“Each cell contains hundreds of mitochondria organelles, and so each can tolerate low levels of mutations in the DNA. But when the proportion reaches high levels, at around 70 percent, then individuals can suffer health problems, including stunted growth, loss of hearing, kidney disease, muscle disease…”

One in 4,000 children born in the United States every year will develop a mitochondrial disorder by age 10. In adults, many diseases of aging have been found to have defects of mitochondrial function. These include, but are not limited to, type 2 diabetes, Parkinson’s disease, atherosclerotic heart disease, stroke, Alzheimer’s disease, and cancer. In addition, many medicines can injure the mitochondria.

In order to prevent the inheritance of such disease-causing mitochondria, couples currently can opt for in-vitro fertilization using a donor’s egg. In this case, the child will not share any of the mother’s DNA.

They can also opt for pre-implantation genetic diagnosis on their own to select embryos that have the least number of mitochondria with mutations inherited from the mother. But it’s not a guarantee their child will not develop a crippling disorder.

Egli and his team saw the potential for nuclear transfer of the mother’s DNA out of her oocyte into a donor’s, preserving the mother’s genotype for passing on to her offspring.

But as Egli pointed out during the phone conference, it is a complicated process. Previous studies had shown that nuclear transfer between oocytes was possible, but the manipulations led to abnormal development of embryos. “So negative consequences for clinical use was a major concern. Nowhere is this more crucial than in the development of a human being.”

Egli wanted to develop an exchange method without adverse consequences on the egg. “Initially we found that the chromosomes started dividing prematurely, resulting in cells with an abnormal chromosome number. Chromosomes are divided between cells by the microtubule spindle–a spindle that is assembled around the chromosomes about the time when the oocytes are retrieved from the ovary.

“We found that when the spindle is not fully assembled, then the premature segregation of the chromosomes could not occur. This allowed the generation of eggs and embryos with normal chromosome number.”

The team successfully performed the transfer on 25 egg cells in the course of their study.

A key technique in their process was the cooling of the eggs to room temperature before carrying out the nuclear transfer.

And since human cells carry many copies of the mitochondria, it was important to test the ‘new’ egg cell to make sure none of the original mitochondria had passed in any cytoplasm with the nucleus into its new home.

The researchers ‘activated’ the new egg cell (by a process of mild electrical stimulation) and over the course of a year, derived several stem cell lines from the blastocyst that developed.

These cell lines were grown and differentiated into many cell types such as heart cells, neurons and pancreatic beta cells. (Because the egg cell was not fertilized, there was no possibility of the blastocyst developing into a full human embryo.)

When the team examined the stem cells, they found no traces of the genome’s original mitochondria. “This exchange proved stable under various scenarios that have the potential to alter the mitochondrial genotype,” said Egli. “We never observed the reemergence of the old mitochondrial genotype and the mitochondrial functions were normal.”

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This could be an important development for fighting the aging process as well. Even if you’re healthy, mitochondrial defects also accumulate over your lifetime, gradually crippling the energy production of your cells. I read somewhere that the cells of a 70-year old man have 1/3 the energy output of a teenager. Imagine if nuclei from an aged person’s cells could be transferred into younger stem cells with healthier mitochondria. Those stem cells could be reimplanted back into the elderly person, where they could grow as younger healthier tissue. In this way, perhaps some parts of an elderly person’s body could be made younger and healthier again.

Hey, aging is a disorder too, and just about everybody suffers from it. So it’s worth finding a cure.

My understanding from the paper (quoted below) is that, even though one or two of the organelles from the original egg can carry over in the transfer process, they’re outnumbered by the hundreds of mtDNA in the ‘new’ host cell.

“MitochondrialDNA transferred with the nuclear genome was initially detected at levels below 1%, decreasing in blastocysts and stem-cell lines to undetectable levels, and remained undetectable after passaging for more than one year, clonal expansion, differentiation into neurons, cardiomyocytes or b-cells, and after cellular reprogramming.”

I would even point out that there are other species whose mitochondria are believed to be superior and more efficient than our own — whales, birds, and even tortoises. Perhaps it might be worth trying to get hold of some of these better mitochondria and transfer some human nuclear DNA to share a cell with them. We might be able to come up with human tissue that produces energy more efficiently, while having a much longer lifespan than regular human cells.

I think it would be great if human beings could live to 200 years or more. It would allow people to get a lot more accomplished in their lifetimes.